Pathophysiology and Treatment of Hyperoxaluria

Mapping Intimacies ◽

10.2310/uro.11017 ◽

2018 ◽

Author(s):

Robin S Chirackal ◽

John C Lieske

Keyword(s):

Genetic Testing ◽

Calcium Oxalate ◽

Primary Hyperoxaluria ◽

Oxalate Decarboxylase ◽

Ribonucleic Acids ◽

Hydroxypyruvate Reductase ◽

Oxalate Absorption ◽

Degrading Bacteria ◽

Fat Malabsorption ◽

Kidney Liver

Humans cannot degrade oxalate. Thus, oxalate that is generated in the liver and/or absorbed from the intestine must be eliminated by the kidneys. Among genetic causes, primary hyperoxaluria (PH) type 1 is the most common and occurs due to deficiency of hepatic peroxisomal alanine glyoxalate aminotransferase. PH2 is caused by deficiency of lysosomal glyoxalate reductase or hydroxypyruvate reductase, whereas PH3 results from deficiency of mitochondrial 4-hydroxy-2-oxoglutarate aldolase. Enteric hyperoxaluria is caused by excessive colonic oxalate absorption due to any type of fat malabsorption. The diagnosis of hyperoxaluria is based on the history, 24-hour urine studies, and genetic testing. Early diagnosis and timely intervention are essential. To treat PH, adequate fluid intake, inhibitors of calcium oxalate crystallization (citrate or neutral phosphorus), and pyridoxine-in responsive patients are all important. Intensive dialysis and prompt kidney or combined kidney-liver transplantation are essential to minimize systemic oxalosis if renal failure occurs. Dietary modifications (low fat, low oxalate, and adequate calcium) are key for enteric hyperoxaluria. Calcium can be used as an oxalate binder. Newer modalities including oxalate degrading bacteria, oral oxalate decarboxylase preparations, and inhibitory ribonucleic acids are all under investigation. This review contains 9 figures, 6 tables, and 90 references. Key Words: bariatric surgery, calcium oxalate, dialysis, enteric hyperoxaluria, fat malabsorption, genetic testing, kidney stone, nephrolithiasis, oxalate, oxalate decarboxylase, Oxalobacter formigenes, primary hyperoxaluria, pyridoxine, transplantation, urolithiasis

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Secretion of Biologically Active Heterologous Oxalate Decarboxylase (OxdC) inLactobacillus plantarumWCFS1 Using Homologous Signal Peptides

BioMed Research International ◽

10.1155/2013/280432 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Ponnusamy Sasikumar ◽

Sivasamy Gomathi ◽

Kolandaswamy Anbazhagan ◽

Govindan Sadasivam Selvam

Keyword(s):

Calcium Oxalate ◽

Recombinant Strain ◽

Specific Activity ◽

Treatment Options ◽

Functional Expression ◽

Biologically Active ◽

Signal Peptides ◽

Oxalate Decarboxylase ◽

Calcium Oxalate Stone ◽

Degrading Bacteria

Current treatment options for patients with hyperoxaluria and calcium oxalate stone diseases are limited and do not always lead to sufficient reduction in urinary oxalate excretion. Oxalate degrading bacteria have been suggested for degrading intestinal oxalate for the prevention of calcium oxalate stone. Here, we reported a recombinantLactobacillus plantarumWCFS1 (L. plantarum) secreting heterologous oxalate decarboxylase (OxdC) that may provide possible therapeutic approach by degrading intestinal oxalate. The results showed secretion and functional expression of OxdC protein inL. plantarumdriven by signal peptides Lp_0373 and Lp_3050. Supernatant of the recombinant strain containing pLp_0373sOxdC and pLp_3050sOxdC showed OxdC activity of 0.05 U/mg and 0.02 U/mg protein, while the purified OxdC from the supernatant showed specific activity of 18.3 U/mg and 17.5 U/mg protein, respectively. The concentration of OxdC protein in the supernatant was 8–12 μg/mL. The recombinant strain showed up to 50% oxalate reduction in medium containing 10 mM oxalate. In conclusion, the recombinantL. plantarumharboring pLp_0373sOxdC and pLp_3050sOxdC can express and secrete functional OxdC and degrade oxalate up to 50% and 30%, respectively.

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[13C2]oxalate absorption in children with idiopathic calcium oxalate urolithiasis or primary hyperoxaluria

Kidney International ◽

10.1038/ki.2008.63 ◽

2008 ◽

Vol 73 (10) ◽

pp. 1181-1186 ◽

Cited By ~ 30

Author(s):

P. Sikora ◽

G.E. von Unruh ◽

B. Beck ◽

M. Feldkötter ◽

M. Zajączkowska ◽

...

Keyword(s):

Calcium Oxalate ◽

Primary Hyperoxaluria ◽

Calcium Oxalate Urolithiasis ◽

Oxalate Absorption

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Hydroxyproline metabolism in mouse models of primary hyperoxaluria

AJP Renal Physiology ◽

10.1152/ajprenal.00473.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. F688-F693 ◽

Cited By ~ 22

Author(s):

John Knight ◽

Ross P. Holmes ◽

Scott D. Cramer ◽

Tatsuya Takayama ◽

Eduardo Salido

Keyword(s):

Renal Function ◽

Calcium Oxalate ◽

Mouse Models ◽

Stone Formation ◽

Genetic Diseases ◽

Primary Hyperoxaluria ◽

Significant Loss ◽

Hydroxypyruvate Reductase ◽

Glyoxylate Metabolism ◽

Liver And Kidney

Primary hyperoxaluria type 1 (PH1) and type 2 (PH2) are rare genetic diseases that result from deficiencies in glyoxylate metabolism. The increased oxalate synthesis that occurs can lead to kidney stone formation, deposition of calcium oxalate in the kidney and other tissues, and renal failure. Hydroxyproline (Hyp) catabolism, which occurs mainly in the liver and kidney, is a prominent source of glyoxylate and could account for a significant portion of the oxalate produced in PH. To determine the sensitivity of mouse models of PH1 and PH2 to Hyp-derived oxalate, animals were fed diets containing 1% Hyp. Urinary excretions of glycolate and oxalate were used to monitor Hyp catabolism and the kidneys were examined to assess pathological changes. Both strains of knockout (KO) mice excreted more oxalate than wild-type (WT) animals with Hyp feeding. After 4 wk of Hyp feeding, all mice deficient in glyoxylate reductase/hydroxypyruvate reductase (GRHPR KO) developed severe nephrocalcinosis in contrast to animals deficient in alanine-glyoxylate aminotransferase (AGXT KO) where nephrocalcinosis was milder and with a lower frequency. Plasma cystatin C measurements over 4-wk Hyp feeding indicated no significant loss of renal function in WT and AGXT KO animals, and significant and severe loss of renal function in GRHPR KO animals after 2 and 4 wk, respectively. These data suggest that GRHPR activity may be vital in the kidney for limiting the conversion of Hyp-derived glyoxylate to oxalate. As Hyp catabolism may make a major contribution to the oxalate produced in PH patients, Hyp feeding in these mouse models should be useful in understanding the mechanisms associated with calcium oxalate deposition in the kidney.

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